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Simultaneous quantitation of urinary cotinine and acrylonitrile-derived mercapturic acids with ultraperformance liquid chromatography–tandem mass spectrometry

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Abstract

Acrylonitrile (AN), a widely used industrial chemical also found in tobacco smoke, has been classified as a possible human carcinogen (group 2B) by the International Agency for Research on Cancer. AN can be detoxified by glutathione S-transferase (GST) to form glutathione (GSH) conjugates in vivo. It can be metabolically activated by cytochrome P450 2E1 to form 2-cyanoethylene oxide, which can also be detoxified by GST to generate GSH conjugates. The GSH conjugates can be further metabolized to mercapturic acids (MAs), namely, N-acetyl-S-(2-cyanoethyl)cysteine (CEMA), N-acetyl-S-(2-hydroxyethyl)cysteine (HEMA), and N-acetyl-S-(1-cyano-2-hydroxyethyl)cysteine (CHEMA). This study developed an ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method to quantitatively profile the major AN urinary metabolites (CEMA, HEMA, and CHEMA) to assess AN exposure, as well as analyze urinary cotinine (COT) as an indicator for tobacco smoke exposure. The limits of quantitation were 0.1, 0.1, 1.0, and 0.05 μg/L for HEMA, CEMA, CHEMA, and COT, respectively. This method was applied to analyze the three AN-derived MAs in 36 volunteers with no prior occupational AN exposure. Data analysis showed significant correlations between the level of COT and the levels of these MAs, suggesting them as biomarkers for exposure to low levels of AN. The results demonstrate that a highly specific and sensitive UPLC-MS/MS method has been successfully developed to quantitatively profile the major urinary metabolites of AN in humans to assess low AN exposure.

Simultaneous quantitation of 3 acrylonitrile-derived mercapturic acids and cotinine in human urine samples with on-line solid-phase extraction LC-MS/MS.

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Acknowledgements

The authors gratefully appreciate the technical support and assistance with the UPLC-MS/MS analyses provided by Dr. Wei-Chung Shih. This study was supported in part by grants from the Institute of Occupational Safety and Health, Council of Labor Affairs (grant no. IOSH98-A313), the National Sciences Council (no. NSC98-2314-B-002-082-MY3), and the Environmental and Occupational Health Center at National Taiwan University, Taiwan.

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Authors and Affiliations

  1. Department of Public Health & Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Rm. 721, No.17, Shiujou Rd, Taipei, 100, Taiwan

    Chia-Fang Wu, Wei-Chung Shih, Yu-Fang Huang & Kuen-Yuh Wu

  2. Division of Analytical Chemistry, Institute of Occupational Safety and Health & Department of Public Health, Fu Jen Catholic University, Council of Labor Affairs, Executive Yuan, Taipei, 22143, Taiwan

    Shi-Nian Uang

  3. School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan

    Su-Yin Chiang

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  1. Chia-Fang Wu
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  2. Shi-Nian Uang
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  3. Su-Yin Chiang
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  4. Wei-Chung Shih
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  5. Yu-Fang Huang
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Correspondence to Kuen-Yuh Wu.

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Chia-Fang Wu and Shi-Nian Uang are co-first authors

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Wu, CF., Uang, SN., Chiang, SY. et al. Simultaneous quantitation of urinary cotinine and acrylonitrile-derived mercapturic acids with ultraperformance liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 402, 2113–2120 (2012). https://doi.org/10.1007/s00216-011-5661-4

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  • DOI: https://doi.org/10.1007/s00216-011-5661-4

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